名 称
　　
化学名：西多福韦 　　

英文名：cidofovir 　　

商品名：Vistide （西多福韦注射液） 　　

规格： 375mg/5ml 　　

适应症：AIDS病人的CMV视网膜炎（巨细胞病毒性视网膜炎）
药理作用
本品被细胞吸收后，在细胞胸苷激酶的作用下转化为活性代谢物单磷酸酯、二磷酸酯和与磷酸胆碱的加成物。西多福韦二磷酸酯通过抑制CMV的DNA聚合酶，竞争性地抑制脱氧胞嘧啶核苷－5＇－三磷酸酯整合入病毒的DNA，减缓DNA的合成，并使病毒DNA失去稳定性，从而抑制病毒的复制。

临床疗效
西多福韦对CMV有高度的抑制活性，对某些耐更昔洛韦或膦甲酸的病毒株也有活性。并对单纯疱疹病毒（HSV）、带状疱疹病毒（VZV）、人类乳头瘤病毒（HPV）等也有很强的活性。与其它抗CMV药物相比，西多福韦的疗效显著且持久，开始使用头两周每周给药一次，此后每两周只需给药一次，使用方便。 　据AntiviraL Research 75(2007)1-13，西多福韦将来注重治疗痘病毒感染及人乳头瘤病毒感染。 　　
优点： 　
w 抑制DNA多聚酶的作用、阻断DNA的合成，而不依赖病毒激酶； 　　
w 抗病毒谱广，包括单纯疱疹病毒、带状疱疹病毒、巨细胞病毒及其他病毒（例如EB病毒、带状疱疹病毒6、腺病毒、乙型肝炎病毒），还包括胸甙激酶耐药株和某些膦甲酸耐药株； 　　
w 用药方便，每周用药1次，持续2周，然后每2周用药1次；无需中心静脉插管（每隔2周，外周静脉插管给药1次）。 　　
缺点：很差的生物利用度，因此只能静注。还有较严重的不可逆肾毒性。 　
w 大多数患者都有发生（53%）； 　　
w 很小的剂量即可发生急性肾功能衰竭； 　　
w 结果导致近曲肾小管细胞损伤和代谢性酸中毒，早期表现为蛋白尿和糖尿； w 肾功能障碍者（肌酐大于1.5mg/dl）为本品使用禁忌证。
药代动力学
在猴肾细胞中，本品的活性代谢物西多福韦二磷酸酯的代谢呈双相性，第一和第二相的消除半衰期分别为24和65小时；另一种代谢物西多福韦单磷酸酯与胆碱的加成物半衰期约为87小时，并可作为西多福韦二磷酸酯的贮存物起作用。 给伴有无症状的CMV感染的HIV阳性男性患者静注本品3或10毫克/千克，一周1次，AUC分别为9.2和24.4毫克/小时/升，终末半衰期分别为4.2和5.9小时，两种剂量的平均血清总清除率每小时约为150毫升/千克。3和10毫克/千克剂量组分别在24及48小时后不能从血浆中测到药物浓度，但其细胞内活性代谢物的半衰期均超过48小时。HIV阳性者分别静注1.0、3.0、5.0、7.5和10毫克/千克的西多福韦，其血药浓度呈双指数下降，总清除半衰期为2.6小时。给药24小时内，剂量的90％以原药形式从尿中排泄。多次给予3.0或10毫克/千克剂量，并不改变药物的药代动力学特性。稳态的分布容积为500毫升/千克，表明药物分布于全身体液。HIV患者口服1.0、3.0或10.0毫克/千克本品，其口服生物利用度小于5.3％；皮下注射1.0或3.0毫克/千克西多福韦的生物利用度可达98％，但在注射部位出现皮下小结和疼痛。
临床研究
100例CD4＋平均计数为6/纳升的AIDS患者和已复发或不能耐受更昔洛韦和膦甲酸治疗的CMV视网膜炎患者，静注两种剂量本品进行随机对照试验。患者一周1次注射5毫克/千克，共两周，其后隔一周注射5毫克/千克（高剂量组）或3毫克/千克（低剂量组），并同时注射丙磺舒4克及两升生理盐水。通过视网膜照相进行评估，两组均能延缓出现新的病损或不使已有的病损加重，而高剂量延缓病情发展的平均时间较低剂量组有显著性差异。 　　
另一组试验，48例AIDS患者和未经治疗的CMV视网膜炎患者随机分为立即治疗组和延迟治疗组。立即治疗组CD4＋平均计数为6/纳升，一周1次静注5毫克/千克，共两周，其后隔一周注射5毫克/千克；延迟治疗组CD4＋平均计数为9/纳升，一旦发展为CMV视网膜炎立即用西多福韦治疗，两个治疗组均同时注射丙磺舒4克和1升生理盐水。结果为，立即治疗组发展为CMV视网膜炎的平均时间为120天，延迟治疗组为22天（P＜0.001）。延迟治疗组在平均时间为19天后开始出现CMV视网膜炎症状的16位患者，经西多福韦治疗后发展为CMV视网膜炎的平均时间为169天（P＝0.002）。
不良反应
患者对本品产生不良反应包括蛋白尿、血清肌酸酐升高、中性白细胞减少、发热和酸中毒。

西多福韦（cidofovir, HPMPC）是新型的胞嘧啶核苷膦酰基甲醚衍生物，由美国Gilead 公司开发。 　　
西多福韦注射液（商品名：Vistide）1996 年首先在美国上市，随后在英、法、意等多国上市。Gilead公司负责Vistide在美国市场的销售，海外市场由合作伙伴Pharmacia Corporation公司（现Pfizer公司）负责。 　　
西多福韦的外用凝胶剂型由Gilead公司开发。在完成I、II期临床后，2004年其上市申请（AIDS病人的难治性HSV感染）被FDA拒绝，原因是临床数据不充分（具体原因不祥）。Gilead已中止了cidofovir外用凝胶制剂的开发(Direct communication, Gilead, 29 Jun 2004)。未见到该公司及其他公司后续开发的报道。 　　
此外，还有个别使用西多福韦滴眼液进行动物模型上抗病毒研究的报道。

WARNING
RENAL IMPAIRMENT IS THE MAJOR TOXICITY OF VISTIDE. CASES OF ACUTE RENAL FAILURE RESULTING IN DIALYSIS AND/OR CONTRIBUTING TO DEATH HAVE OCCURRED WITH AS FEW AS ONE OR TWO DOSES OF VISTIDE. TO REDUCE POSSIBLE NEPHROTOXICITY, INTRAVENOUS PREHYDRATION WITH NORMAL SALINE AND ADMINISTRATION OF PROBENECID MUST BE USED WITH EACH VISTIDE INFUSION. RENAL FUNCTION (SERUM CREATININE AND URINE PROTEIN) MUST BE MONITORED WITHIN 48 HOURS PRIOR TO EACH DOSE OF VISTIDE AND THE DOSE OF VISTIDE MODIFIED FOR CHANGES IN RENAL FUNCTION AS APPROPRIATE (SEE DOSAGE AND ADMINISTRATION). VISTIDE IS CONTRAINDICATED IN PATIENTS WHO ARE RECEIVING OTHER NEPHROTOXIC AGENTS.

NEUTROPENIA HAS BEEN OBSERVED IN ASSOCIATION WITH VISTIDE TREATMENT. THEREFORE, NEUTROPHIL COUNTS SHOULD BE MONITORED DURING VISTIDE THERAPY.

VISTIDE IS INDICATED ONLY FOR THE TREATMENT OF CMV RETINITIS IN PATIENTS WITH ACQUIRED IMMUNODEFICIENCY SYNDROME.

IN ANIMAL STUDIES CIDOFOVIR WAS CARCINOGENIC, TERATOGENIC AND CAUSED HYPOSPERMIA (SEE package insert for CARCINOGENESIS, MUTAGENESIS, & IMPAIRMENT OF FERTILITY

MICROBIOLOGY

Mechanism of Action
Cidofovir suppresses cytomegalovirus (CMV) replication by selective inhibition of viral DNA synthesis. Biochemical data support selective inhibition of CMV DNA polymerase by cidofovir diphosphate, the active intracellular metabolite of cidofovir. Cidofovir diphosphate inhibits herpesvirus polymerases at concentrations that are 8- to 600-fold lower than those needed to inhibit human cellular DNA polymerases alpha, beta, and gamma. Incorporation of cidofovir into the growing viral DNA chain results in reductions in the rate of viral DNA synthesis.

INDICATION AND USAGE
VISTIDE is indicated for the treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (AIDS). THE SAFETY AND EFFICACY OF VISTIDE HAVE NOT BEEN ESTABLISHED FOR TREATMENT OF OTHER CMV INFECTIONS (SUCH AS PNEUMONITIS OR GASTROENTERITIS), CONGENITAL OR NEONATAL CMV DISEASE, OR CMV DISEASE IN NON-HIV-INFECTED INDIVIDUALS

CONTRAINDICATIONS
Initiation of therapy with VISTIDE is contraindicated in patients with a serum creatinine > 1.5 mg/dL, a calculated creatinine clearance 55 mL/min, or a urine protein 100 mg/dL (equivalent to 2+ proteinuria).

VISTIDE is contraindicated in patients receiving agents with nephrotoxic potential. Such agents must be discontinued at least seven days prior to starting therapy with VISTIDE.

VISTIDE is contraindicated in patients with hypersensitivity to cidofovir.

VISTIDE is contraindicated in patients with a history of clinically severe hypersensitivity to probenecid or other sulfa-containing medications.

Direct intraocular injection of VISTIDE is contraindicated; direct injection of cidofovir has been associated with iritis, ocular hypotony, and permanent impairment of vision.


WARNINGS

Nephrotoxicity
Dose-dependent nephrotoxicity is the major dose-limiting toxicity related to VISTIDE administration. Cases of acute renal failure resulting in dialysis and/or contributing to death have occurred with as few as one or two doses of VISTIDE. Renal function (serum creatinine and urine protein) must be monitored within 48 hours prior to each dose of VISTIDE. Dose adjustment or discontinuation is required for changes in renal function (serum creatinine and/or urine protein) while on therapy. Proteinuria, as measured by urinalysis in a clinical laboratory, may be an early indicator of VISTIDE-related nephrotoxicity. Continued administration of VISTIDE may lead to additional proximal tubular cell injury, which may result in glycosuria, decreases in serum phosphate, uric acid, and bicarbonate, elevations in serum creatinine, and/or acute renal failure, in some cases, resulting in the need for dialysis. Patients with these adverse events occurring concurrently and meeting a criteria of Fanconi's syndrome have been reported. Renal function that did not return to baseline after drug discontinuation has been observed in clinical studies of VISTIDE.

Intravenous normal saline hydration and oral probenecid must accompany each VISTIDE infusion. Probenecid is known to interact with the metabolism or renal tubular excretion of many drugs (see PRECAUTIONS). The safety of VISTIDE has not been evaluated in patients receiving other known potentially nephrotoxic agents, such as intravenous aminoglycosides (e.g., tobramycin, gentamicin, and amikacin), amphotericin B, foscarnet, intravenous pentamidine, vancomycin, and non-steroidal anti-inflammatory agents (see DOSAGE AND ADMINISTRATION).


Preexisting Renal Impairment
Initiation of therapy with VISTIDE is contraindicated in patients with a baseline serum creatinine > 1.5 mg/dL, a creatinine clearance 55 mL/min, or a urine protein 100 mg/dL (equivalent to 2+ proteinuria).


Hematological Toxicity
Neutropenia may occur during VISTIDE therapy. Neutrophil count should be monitored while receiving VISTIDE therapy.


Decreased Intraocular Pressure/Ocular Hypotony
Decreased intraocular pressure may occur during VISTIDE therapy, and in some instances has been associated with decreased visual acuity. Intraocular pressure should be monitored during VISTIDE therapy.


Metabolic Acidosis
Decreased serum bicarbonate associated with proximal tubule injury and renal wasting syndrome (including Fanconi's syndrome) have been reported in patients receiving VISTIDE (see ADVERSE REACTIONS). Cases of metabolic acidosis in association with liver dysfunction and pancreatitis resulting in death have been reported in patients receiving VISTIDE.



PRECAUTIONS

General
Due to the potential for increased nephrotoxicity, doses greater than the recommended dose must not be administered and the frequency or rate of administration must not be exceeded (see DOSAGE AND ADMINISTRATION).

VISTIDE is formulated for intravenous infusion only and must not be administered by intraocular injection. Administration of VISTIDE by infusion must be accompanied by oral probenecid and intravenous saline prehydration (see DOSAGE AND ADMINISTRATION).


Uveitis/Iritis
Uveitis or iritis was reported in clinical trials and during postmarketing in patients receiving VISTIDE therapy. Treatment with topical corticosteroids with or without topical cycloplegic agents should be considered. Patients should be monitored for signs and symptoms of uveitis/iritis during VISTIDE therapy.


Information for Patients
Patients should be advised that VISTIDE is not a cure for CMV retinitis, and that they may continue to experience progression of retinitis during and following treatment. Patients receiving VISTIDE should be advised to have regular follow-up ophthalmologic examinations. Patients may also experience other manifestations of CMV disease despite VISTIDE therapy.

HIV-infected patients may continue taking antiretroviral therapy, but those taking zidovudine should be advised to temporarily discontinue zidovudine administration or decrease their zidovudine dose by 50%, on days of VISTIDE administration only, because probenecid reduces metabolic clearance of zidovudine.

Patients should be informed of the major toxicity of VISTIDE, namely renal impairment, and that dose modification, including reduction, interruption, and possibly discontinuation, may be required. Close monitoring of renal function (routine urinalysis and serum creatinine) while on therapy should be emphasized.

The importance of completing a full course of probenecid with each VISTIDE dose should be emphasized. Patients should be warned of potential adverse events caused by probenecid (e.g., headache, nausea, vomiting, and hypersensitivity reactions). Hypersensitivity/allergic reactions may include rash, fever, chills and anaphylaxis. Administration of probenecid after a meal or use of antiemetics may decrease the nausea. Prophylactic or therapeutic antihistamines and/or acetaminophen can be used to ameliorate hypersensitivity reactions.

Patients should be advised that cidofovir causes tumors, primarily mammary adenocarcinomas, in rats. VISTIDE should be considered a potential carcinogen in humans (See Carcinogenesis, Mutagenesis, & Impairment of Fertility). Women should be advised of the limited enrollment of women in clinical trials of VISTIDE.

Patients should be advised that VISTIDE caused reduced testes weight and hypospermia in animals. Such changes may occur in humans and cause infertility. Women of childbearing potential should be advised that cidofovir is embryotoxic in animals and should not be used during pregnancy. Women of childbearing potential should be advised to use effective contraception during and for 1 month following treatment with VISTIDE. Men should be advised to practice barrier contraceptive methods during and for 3 months after treatment with VISTIDE.


Drug Interactions

Probenecid
Probenecid is known to interact with the metabolism or renal tubular excretion of many drugs (e.g., acetaminophen, acyclovir, angiotensin-converting enzyme inhibitors, aminosalicylic acid, barbiturates, benzodiazepines, bumetanide, clofibrate, methotrexate, famotidine, furosemide, nonsteroidal anti-inflammatory agents, theophylline, and zidovudine). Concomitant medications should be carefully assessed. Zidovudine should either be temporarily discontinued or decreased by 50% when coadministered with probenecid on the day of VISTIDE infusion.


Nephrotoxic agents
Concomitant administration of VISTIDE and agents with nephrotoxic potential [e.g., intravenous aminoglycosides (e.g., tobramycin, gentamicin, and amikacin), amphotericin B, foscarnet, intravenous pentamidine, vancomycin, and nonsteroidal anti-inflammatory agents] is contraindicated. Such agents must be discontinued at least seven days prior to starting therapy with VISTIDE.


Carcinogenesis, Mutagenesis, & Impairment of Fertility
Chronic, two-year carcinogenicity studies in rats and mice have not been carried out to evaluate the carcinogenic potential of cidofovir. However, a 26-week toxicology study evaluating once weekly subscapular subcutaneous injections of cidofovir in rats was terminated at 19 weeks because of the induction, in females, of palpable masses, the first of which was detected after six doses. The masses were diagnosed as mammary adenocarcinomas which developed at doses as low as 0.6 mg/kg/week, equivalent to 0.04 times the human systemic exposure at the recommended intravenous VISTIDE dose based on AUC comparisons.

In a 26-week intravenous toxicology study in which rats received 0.6, 3, or 15 mg/kg cidofovir once weekly, a significant increase in mammary adenocarcinomas in female rats as well as a significant incidence of Zymbal's gland carcinomas in male and female rats were seen at the high dose but not at the lower two doses. The high dose was equivalent to 1.1 times the human systemic exposure at the recommended dose of VISTIDE, based on comparisons of AUC measurements. In light of the results of these studies, cidofovir should be considered to be a carcinogen in rats as well as a potential carcinogen in humans.

Cynomolgus monkeys received intravenous cidofovir, alone and in conjunction with concomitant oral probenecid, intravenously once weekly for 52 weeks at doses resulting in exposures of approximately 0.7 times the human systemic exposure at the recommended dose of VISTIDE. No tumors were detected. However, the study was not designed as a carcinogenicity study due to the small number of animals at each dose and the short duration of treatment.

No mutagenic response was observed in microbial mutagenicity assays involving Salmonella typhimurium (Ames) and Escherichia coli in the presence and absence of metabolic activation. An increase in micronucleated polychromatic erythrocytes in vivo was seen in mice receiving 2000 mg/kg, a dosage approximately 65-fold higher than the maximum recommended clinical intravenous VISTIDE dose based on body surface area estimations. Cidofovir induced chromosomal aberrations in human peripheral blood lymphocytes in vitro without metabolic activation. At the 4 cidofovir levels tested, the percentage of damaged metaphases and number of aberrations per cell increased in a concentration-dependent manner.

Studies showed that cidofovir caused inhibition of spermatogenesis in rats and monkeys. However, no adverse effects on fertility or reproduction were seen following once weekly intravenous injections of cidofovir in male rats for 13 consecutive weeks at doses up to 15 mg/kg/week (equivalent to 1.1 times the recommended human dose based on AUC comparisons). Female rats dosed intravenously once weekly at 1.2 mg/kg/week (equivalent to 0.09 times the recommended human dose based on AUC) or higher, for up to 6 weeks prior to mating and for 2 weeks post mating had decreased litter sizes and live births per litter and increased early resorptions per litter. Peri- and post-natal development studies in which female rats received subcutaneous injections of cidofovir once daily at doses up to 1.0 mg/kg/day from day 7 of gestation through day 21 postpartum (approximately 5 weeks) resulted in no adverse effects on viability, growth, behavior, sexual maturation or reproductive capacity in the offspring.


Pregnancy
Category C
Cidofovir was embryotoxic (reduced fetal body weights) in rats at 1.5 mg/kg/day and in rabbits at 1.0 mg/kg/day, doses which were also maternally toxic, following daily intravenous dosing during the period of organogenesis. The no-observable-effect levels for embryotoxicity in rats (0.5 mg/kg/day) and in rabbits (0.25 mg/kg/day) were approximately 0.04 and 0.05 times the clinical dose (5 mg/kg every other week) based on AUC, respectively. An increased incidence of fetal external, soft tissue and skeletal anomalies (meningocele, short snout, and short maxillary bones) occurred in rabbits at the high dose (1.0 mg/kg/day) which was also maternally toxic. There are no adequate and well-controlled studies in pregnant women. VISTIDE should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.


Nursing Mothers
It is not known whether cidofovir is excreted in human milk. Since many drugs are excreted in human milk and because of the potential for adverse reactions as well as the potential for tumorigenicity shown for cidofovir in animal studies, VISTIDE should not be administered to nursing mothers. The U.S. Public Health Service Centers for Disease Control and Prevention advises HIV-infected women not to breast-feed to avoid postnatal transmission of HIV to a child who may not yet be infected.


Pediatric Use
Safety and effectiveness in children have not been studied. The use of VISTIDE in children with AIDS warrants extreme caution due to the risk of long-term carcinogenicity and reproductive toxicity. Administration of VISTIDE to children should be undertaken only after careful evaluation and only if the potential benefits of treatment outweigh the risks.


Geriatric Use
No studies of the safety or efficacy of VISTIDE in patients over the age of 60 have been conducted. Since elderly individuals frequently have reduced glomerular filtration, particular attention should be paid to assessing renal function before and during VISTIDE administration (see DOSAGE AND ADMINISTRATION).


OVERDOSAGE
Two cases of cidofovir overdose have been reported. These patients received single doses of VISTIDE at 16.3 mg/kg and 17.4 mg/kg, respectively, with concomitant oral probenecid and intravenous hydration. In both cases, the patients were hospitalized and received oral probenecid (one gram three times daily) and vigorous intravenous hydration with normal saline for 3 to 5 days. Significant changes in renal function were not observed in either patient.


DOSAGE AND ADMINISTRATION
VISTIDE MUST NOT BE ADMINISTERED BY INTRAOCULAR INJECTION.

Dosage
THE RECOMMENDED DOSAGE, FREQUENCY, OR INFUSION RATE MUST NOT BE EXCEEDED. VISTIDE MUST BE DILUTED IN 100 MILLILITERS 0.9% (NORMAL) SALINE PRIOR TO ADMINISTRATION. TO MINIMIZE POTENTIAL NEPHROTOXICITY, PROBENECID AND INTRAVENOUS SALINE PREHYDRATION MUST BE ADMINISTERED WITH EACH VISTIDE INFUSION.


Induction Treatment
The recommended induction dose of VISTIDE for patients with a serum creatinine of 1.5 mg/dL, a calculated creatinine clearance > 55 mL/min, and a urine protein < 100 mg/dL (equivalent to < 2+ proteinuria) is 5 mg/kg body weight (given as an intravenous infusion at a constant rate over 1 hr) administered once weekly for two consecutive weeks. Because serum creatinine in patients with advanced AIDS and CMV retinitis may not provide a complete picture of the patient's underlying renal status, it is important to utilize the Cockcroft-Gault formula to more precisely estimate creatinine clearance (CrCl). As creatinine clearance is dependent on serum creatinine and patient weight, it is necessary to calculate clearance prior to initiation of VISTIDE.
CrCl (mL/min) should be calculated according to the following formula:

Creatinine clearance for males =	[140-age (years)]× [body wt (kg)] 72 × [serum creatinine (mg/dL)]
Creatinine clearance for females =	[140-age (years)]× [body wt (kg)]× 0.85 72 × [serum creatinine (mg/dL)]

Maintenance Treatment
The recommended maintenance dose of VISTIDE is 5 mg/kg body weight (given as an intravenous infusion at a constant rate over 1 hr), administered once every 2 weeks.


Dose Adjustment

Changes in Renal Function During VISTIDE Therapy
The maintenance dose of VISTIDE must be reduced from 5 mg/kg to 3 mg/kg for an increase in serum creatinine of 0.3 – 0.4 mg/dL above baseline. VISTIDE therapy must be discontinued for an increase in serum creatinine of 0.5 mg/dL above baseline or development of 3+ proteinuria.


Preexisting Renal Impairment
VISTIDE is contraindicated in patients with a serum creatinine concentration > 1.5 mg/dL, a calculated creatinine clearance 55 mL/min, or a urine protein 100 mg/dL (equivalent to 2+ proteinuria).


Probenecid
Probenecid must be administered orally with each VISTIDE dose. Two grams must be administered 3 hr prior to the VISTIDE dose and one gram administered at 2 and again at 8 hr after completion of the 1 hr VISTIDE infusion (for a total of 4 grams).

Ingestion of food prior to each dose of probenecid may reduce drug-related nausea and vomiting. Administration of an antiemetic may reduce the potential for nausea associated with probenecid ingestion. In patients who develop allergic or hypersensitivity symptoms to probenecid, the use of an appropriate prophylactic or therapeutic antihistamine and/or acetaminophen should be considered (see CONTRAINDICATIONS).


Hydration
Patients must receive at least one liter of 0.9% (normal) saline solution intravenously with each infusion of VISTIDE. The saline solution should be infused over a 1–2 hr period immediately before the VISTIDE infusion. Patients who can tolerate the additional fluid load should receive a second liter. If administered, the second liter of saline should be initiated either at the start of the VISTIDE infusion or immediately afterwards, and infused over a 1 to 3 hr period.


Method of Preparation and Administration
Inspect vials visually for particulate matter and discoloration prior to administration. If particulate matter or discoloration is observed, the vial should not be used. With a syringe, extract the appropriate volume of VISTIDE from the vial and transfer the dose to an infusion bag containing 100 mL 0.9% (normal) saline solution. Infuse the entire volume intravenously into the patient at a constant rate over a 1 hr period. Use of a standard infusion pump for administration is recommended.

It is recommended that VISTIDE infusion admixtures be administered within 24 hr of preparation and that refrigerator or freezer storage not be used to extend this 24 hr limit.

If admixtures are not intended for immediate use, they may be stored under refrigeration (2–8°C) for no more than 24 hr. Refrigerated admixtures should be allowed to equilibrate to room temperature prior to use.

The chemical stability of VISTIDE admixtures was demonstrated in polyvinyl chloride composition and ethylene/propylene copolymer composition commercial infusion bags, and in glass bottles. No data are available to support the addition of other drugs or supplements to the cidofovir admixture for concurrent administration.

VISTIDE is supplied in single-use vials. Partially used vials should be discarded (see Handling and Disposal).

Compatibility with Ringer's solution, Lactated Ringer's solution or bacteriostatic infusion fluids has not been evaluated.


Handling and Disposal
Due to the mutagenic properties of cidofovir, adequate precautions including the use of appropriate safety equipment are recommended for the preparation, administration, and disposal of VISTIDE. The National Institutes of Health presently recommends that such agents be prepared in a Class II laminar flow biological safety cabinet and that personnel preparing drugs of this class wear surgical gloves and a closed front surgical-type gown with knit cuffs. If VISTIDE contacts the skin, wash membranes and flush thoroughly with water. Excess VISTIDE and all other materials used in the admixture preparation and administration should be placed in a leak-proof, puncture-proof container. The recommended method of disposal is high temperature incineration.


Patient Monitoring
Serum creatinine and urine protein must be monitored within 48 hours prior to each dose. White blood cell counts with differential should be monitored prior to each dose. In patients with proteinuria, intravenous hydration should be administered and the test repeated. Intraocular pressure, visual acuity and ocular symptoms should be monitored periodically.


HOW SUPPLIED
VISTIDE (cidofovir injection) 75 mg/mL for intravenous infusion, is supplied as a non-preserved solution in single-use clear glass vials as follows:

NDC 61958-0101-1 375 mg in a 5 mL vial in a single-unit carton

VISTIDE should be stored at controlled room temperature 20°–25°C (68°–77°F).